CSF B Cells Characterized in Virus-Associated Diseases

Regulation of the local immune response is crucial in protecting the central nervous system (CNS) from viral infection and immunopathologically mediated tissue damage.

Intrathecal antibody synthesis is a well-documented phenomenon in infectious neurological diseases as well as in demyelinating diseases, but little is known about the role of B cells in the central nervous systems.


Scientists at the US National Institute of Neurological Disorders and Stroke (Bethesda, MD, USA) and their colleagues examined B cell and T cell immunophenotypes in cerebral spinal fluid (CSF) of patients with Human T cell lymphotropic virus 1 (HTLV)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) compared to healthy normal donors and subjects with the other chronic virus infection and/or neuroinflammatory diseases including human immunodeficiency virus (HIV) infection, multiple sclerosis (MS) and progressive multifocal leukoencephalopathy.

A total of 71 HAM/TSP patients and 12 HTLV-1-positive asymptomatic carriers (ACs) were evaluated according to established criteria. Luciferase Immunoprecipitation Systems (LIPS) assay were performed on serum, CSF samples or B cell culture supernatants. For analysis of peripheral blood lymphocyte and CSF lymphocyte populations, EDTA-treated whole blood or CSF cells were stained for a multiplicity of immunological antigens. All flow cytometric analysis was performed using a LSR II flow cytometer. HTLV-1 pro-viral load (PVL) was measured using droplet digital PCR. Interleukin-21 (IL-21) was detected in serum and CSF samples of HAM/TSP patients and ACs using Human Legend Max Human IL-21 ELISA kit.

The investigators found that antibody secreting B cells (ASCs) were elevated in HAM/TSP patients, which were significantly correlated with intrathecal HTLV-1-specific antibody responses. High frequency of ASCs was also detected in patients with relapsing-remitting multiple sclerosis (RRMS). While RRMS patients showed significant correlations between ASCs and memory follicular helper CD4+ T cells, CD4+CD25+ T cells were elevated in HAM/TSP patients, which were significantly correlated with ASCs and HTLV-1 proviral load.

The authors concluded that their results highlight the importance of the B cell compartment and the associated inflammatory milieu in HAM/TSP patients where virus-specific antibody production may be required to control viral persistence and/or may be associated with disease development. The study was published on April 30, 2018, in the journal PLoS Pathogens.

Related Links:
US National Institute of Neurological Disorders and Stroke